Cancer patients have a heightened incidence of coagulopathies and frequently exhibit deposits of fibrin-gel at sites of solid tumor growth. Neither the nature of this fibrin nor its biological significance is presently understood. The term "fibrin" itself is relatively nonspecific and can refer to soluble or insoluble monomers or polymers joined together in any of several configurations; these different molecular entities may have very different biological properties. Any examination of fibrin's role in tumor biology must also consider a possible role for fibronectin, a protein found circulating in the blood and present on the surfaces of many cells. Fibronectin has binding sites for fibrin and is commonly associated with fibrin in tissue injury. The goals of this proposal are to characterize the fibrin and fibronectin deposited about tumors, to measure its accumulation and catabolism, and to evaluate its biological significance. To accomplish these goals, we will employ purified homologous fibrinogen and plasma fibronectin as radiolabelled probes to elucidate the biochemical configuration(s) of fibrin/fibronectin accumulating about tumors, as well as their rates of influx, turnover, and efflux. Other more biologically oriented studies will evaluate the significance of these events. We will 1. Determine whether fibrin/fibronectin gels provide a physical barrier to host leukocyte migration and to subsequent target tumor cell killing. 2. Relate tumor associated fibrin/fibronectin deposition and degradation to tumor growth, angiogenesis and desmoplasia.